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Review
. 2018 Aug 28;2(16):2159-2175.
doi: 10.1182/bloodadvances.2018016493.

Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation

Kaiwen Chen  1   2 , Matthew P Cheng  1   2 , Sarah P Hammond  1   2 , Hermann Einsele  3 , Francisco M Marty  1   2
Affiliations
Review

Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation

Kaiwen Chen et al. Blood Adv. .

Abstract

Patients treated with allogeneic hematopoietic cell transplantation (HCT) are at risk of cytomegalovirus (CMV) reactivation and disease, which results in increased morbidity and mortality. Although universal antiviral prophylaxis against CMV improves outcomes in solid organ transplant recipients, data have been conflicting regarding such prophylaxis in patients undergoing allogeneic HCT. We conducted a systematic review of randomized trials of prophylactic antivirals against CMV after allogeneic HCT to summarize the evolution of the field over the last 35 years and evaluate the prophylactic potential of antiviral agents against CMV after allogeneic HCT. Electronic databases were queried from database inception through 31 December 2017. For included studies, incidence of CMV infection and all-cause mortality were collected as primary outcomes; CMV disease incidence, use of preemptive therapy, and drug toxicities were collected as secondary outcomes. Nineteen clinical trials conducted between 1981 and 2017 involving a total of 4173 patients were included for review. Prophylactic strategies included use of acyclovir, valacyclovir, ganciclovir, maribavir, brincidofovir, and letermovir compared with placebo or a comparator antiviral. Fourteen trials that compared antiviral prophylaxis with placebo demonstrated overall effectiveness in reducing incidence of CMV infection (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.42-0.58), CMV disease (OR, 0.56; 95% CI, 0.40-0.80), and use of preemptive therapy (OR, 0.51; 95% CI, 0.42-0.62; 6 trials); however, none demonstrated reduction in all-cause mortality (OR, 0.96; 95% CI, 0.78-1.18) except the phase 3 trial of letermovir (week-24 OR, 0.59; 95% CI, 0.38-0.98). Additional research is warranted to determine patient groups most likely to benefit from antiviral prophylaxis and its optimal deployment after allogeneic HCT.

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Conflict of interest statement

Conflict-of-interest disclosure: S.P.H. has received institutional research support from Merck. H.E. has participated in advisory boards for Chimerix, Clinicgene, and Merck. F.M.M. has received institutional research support from Astellas, Chimerix, Merck, and Shire and consulting honoraria from Alexion, Chimerix, Fate Therapeutics, GlaxoSmithKline, LFB, Merck, Roche Molecular Diagnostics, and Shire. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Systematic review flow diagram.
Figure 2.
Figure 2.
Timelines of trials reviewed.
Figure 3.
Figure 3.
Forest plots summarizing outcomes of trials of antiviral prophylaxis vs placebo in HCT patients. (A) All-cause mortality. (B) CMV disease. (C) CMV infection (reactivation). (D) Preemptive therapy. BID, twice per day; df, degree of freedom.
Figure 3.
Figure 3.
Forest plots summarizing outcomes of trials of antiviral prophylaxis vs placebo in HCT patients. (A) All-cause mortality. (B) CMV disease. (C) CMV infection (reactivation). (D) Preemptive therapy. BID, twice per day; df, degree of freedom.
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